Issue link: https://viewer.e-digitaledition.com/i/51232
RECENT RESEARCH New Therapy Marks a Milestone in Fight Against Cystic Fibrosis Results of a pivotal Phase 3 clinical trial published in the Nov. 3, 2011, New England Journal of Medicine, find that the oral medication ivacaftor (VX-770) provides major, sustained improve- ment in lung function, growth and other signs and symptoms for cystic fibrosis (CF) patients. The multi-site study marks the first time a drug has been shown to work on the disease process rather than on the symptoms. CF, which has no cure, is the most common lethal genetic disease in Caucasians. Ivacaf tor, a drug developed by Vertex Pharmaceuticals, targets the underlying cause of CF, with the goal of preventing or slowing the development of related complications. Ivacaftor is a "potentiator" of the mutant CF transmembrane conductance regulator (CFTR) protein — the fundamental defect in cystic fibrosis — and acts by restoring the balance of salt and water on the surface of the airways. The pivotal Phase 3 clinical trial, conducted in 161 people with CF ages 12 years and older with a specific CF mutation known as G551D (affecting 4 percent of people with CF), showed that taking the oral medication twice daily for 48 weeks improved several key outcome measures of CF, including lung function, growth and sweat chloride levels. "We have been treating cystic fibro- sis for more than 60 years. Current therapies are directed at the complica- tions of the disease. This drug targets the basic defect of cystic fibrosis," says Michael W. Konstan, MD, one of the study's co-authors and chairman of the Department of Pediatrics at Case Western Reserve University School of Medicine and University Hospitals (UH) Rainbow Babies & Children's Hospital. Dr. Konstan is also director of the LeRoy W. Matthews Cystic Fibrosis Center at UH Rainbow Babies & Children's Hospital. "Our hope is that by treating the basic defect, one can prevent complica- tions of the disease, with the ultimate goal of improving the life span of people with CF," he says. Same Gene has Opposite Effects in Prostate, Breast Cancers Researchers at Cleveland Clinic have discovered that a gene – known as an androgen receptor (AR) — is found in both prostate and breast cancers yet has opposite effects on these diseases. In prostate cancer, the AR gene pro- motes cancer growth when the gene is "turned on." In breast cancer, the AR gene promotes cancer growth when the gene is "turned off," as is often the case after menopause, when AR production ceases in women. What this means is that treating prostate and breast cancers require completely opposite approaches to AR. In treating prostate cancer, the strategy should be to block AR; in breast cancer, the strategy should be to support AR production. Researchers from Cleveland Clinic's Lerner Research Institute, including Charis Eng, MD, PhD, chair, Genomic Medicine Institute; Robert Silverman, PhD, and Warren Heston, PhD, both of the Department of Cancer Biology; focused on whether the androgen receptor (AR) molecule offers evidence of the tumor suppressor protein PTEN. The research discovered that AR inhib- its PTEN expression in prostate cancer cells, but stimulates it in breast cancer cells. The conclusions, published in the October 21, 2011 issue of Oncogene, explain why prostate cancer progres- sion is associated with increased AR expression (and a common prostate cancer treatment strategy involves blocking AR), while most breast cancers occur post-menopause, after AR production has ceased (making AR supplementation a strategy for treating breast cancer). "We now see how androgen affects PTEN expression — and ultimately cancer," says Dr. Eng. "Our observa- tions help explain why this prostate cancer risk can be halved by drinking 30 | Cleveland-Akron-Canton MD NEWS MDNEWS.COM JANUARY-FEBRUARY 2012